Oncology Commons^™

New Interleukin-15 Superagonist (Il-15sa) Significantly Enhances Graft-Versus-Tumor Activity., Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Md, Onder Alpdogan

Department of Medical Oncology Faculty Papers

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the ...

Oncology Section Edge Task Force On Urogenital Cancer Outcomes: Clinical Measures Of Lymphedema—A Systematic Review, Joy C. Cohn, Hannah Geyer, Jeannette Lee, Mary Insana Fisher

Physical Therapy Faculty Publications

Background: Valid and reliable tools to assess lymphedema are necessary to accurately evaluate status and to objectively document and measure the results of interventions. Understanding the advantages and disadvantages of each measure can inform the clinician's choice of the appropriate tool to be used in the clinic or research setting.

Purpose: To identify reliable and valid measurement techniques that are sensitive to change for assessing edema volume or soft tissue change in the lower extremities or genital region of patients with lymphedema.

Methods: A systematic review of the literature was conducted to assess the published psychometric properties and clinical ...

Metastatic Squamous Cell Carcinoma To The Colon Arising From A Mature Cystic Ovarian Teratoma, Jaimie Maines, Jordan Newell, Elizabeth Frauenhoffer, Justin Juliano, Francesca Ruggiero, Ian Schreibman, Joshua P. Kesterson

Proceedings in Obstetrics and Gynecology

Malignant transformation of a mature cystic teratoma is extremely rare, occurring in 0.17-2% of cases.¹ The most common malignant degeneration is squamous cell carcinoma (SCC) arising from the ectoderm. Approximately half of all cases of SCC of the ovary are confined to the ovary at time diagnosis.^1,2 Secondary to its absolute rarity and the relative infrequency of cases with metastatic spread the optimal treatment of advanced stage disease is unknown. Outcomes for locally advanced and widespread disease have historically been very poor. Ford and Timmons recently reported on a patient with stage IIC SCC arising in ...

A Phase Ii Randomized Trial Of Observation Versus Stereotactic Ablative Radiation For Oligometastatic Prostate Cancer (Oriole)., Noura Radwan, Ryan Phillips, Ashley Ross, Steven P. Rowe, Michael A. Gorin, Emmanuel S. Antonarakis, Curtiland Deville, Stephen Greco, Samuel Denmeade, Channing Paller, Daniel Y. Song, Maximilian Diehn, Hao Wang, Michael Carducci, Kenneth J. Pienta, Martin G. Pomper, Theodore L. Deweese, Adam Dicker, Mario Eisenberger, Phuoc T. Tran

Department of Radiation Oncology Faculty Papers

BACKGROUND: We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy ...

Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta

Kathleen C. Brown

Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.

Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin ...

The Flavonoid Nobiletin Inhibits Tumor Growth And Angiogenesis Of Ovarian Cancers Via The Akt Pathway, Jianchu Chen, Allen Y. Chen, Haizhi Huang, Xingqian Ye, William D. Rollyson, Haley E. Perry, Kathleen C. Brown, Yon Rojanasakul, Gary O. Rankin, Piyali Dasgupta, Yi Charlie Chen

Kathleen C. Brown

Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving ...

Discoidin Domain Receptor 1 Modulates Insulin Receptor Signaling And Biological Responses In Breast Cancer Cells., Veronica Vella, Roberta Malaguarnera, Maria Luisa Nicolosi, Chiara Palladino, Cristina Spoleti, Michele Massimino, Paolo Vigneri, Michele Purrello, Marco Ragusa, Andrea Morrione, Antonino Belfiore

Department of Urology Faculty Papers

The fetal isoform A of the insulin receptor (IR-A) is frequently overexpressed in a variety of malignancies including breast cancer. IR overexpression has a recognized role in cancer progression and resistance to anticancer therapies. In particular, IR-A has a peculiar mitogenic potential and is activated not only by insulin but also by IGF-2. Previously, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis.We now evaluated whether DDR1 is able to exert a role in ...

Multiple Myeloma Vaccination Patterns In A Large Health System: A Pilot Study, Andinet Alemu, Maharaj Singh, Chris Blumberg, John O. Richards, Martin K. Oaks, Michael A. Thompson

Aurora Internal Medicine Residents

Purpose Common reasons for hospitalization and death in patients with multiple myeloma (MM) are infections. As patients with MM are living longer and are treated with immunomodulatory drugs, there is a need to immunize against vaccine-preventable diseases and ultimately determine the efficacy of these vaccines. We evaluated vaccination practice patterns in MM patients at our health system using electronic medical records and data analytics. Methods This institutional review board-approved study retrospectively reviewed patients with MM who visited the health system from May 2012 to May 2014. Data collected included demographics, influenza vaccination (FV) and pneumonia vaccination (PV) history, hospitalization episodes ...

Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie

Honors College Capstone Experience/Thesis Projects

With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay ...

Establishment Of An Orthotopic Patient-Derived Xenograft Mouse Model Using Uveal Melanoma Hepatic Metastasis., Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Michael J. Mastrangelo, Paolo Fortina, Andrew E. Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment. To overcome these limitations, we developed a ...

Chemical Modulation Of Cancer Cells To Enhance Tumor Immunity, Florisela Herrejon Chavez

PSU McNair Scholars Online Journal

Breakthroughs in immunotherapy have led to cancer therapeutics that activate the immune system by blocking inhibitory mechanisms. This class of therapeutics has resulted in longer survival rates for cancer patients, some living over 10 years after being diagnosed as terminally ill. However, only a small fraction of patients who receive immunotherapy drugs respond favorably.Recent studies suggest that certain anticancer agents (both cytotoxic chemotherapeutics and targeted drugs) stimulate immune recognition of cancers. Identification of such immunomodulatory anticancer agents would make ideal partners for current immunotherapy treatments, thus increasing the proportion of the treated patients who benefit from immunotherapy. This study ...

Multiple Myeloma Vaccination Patterns In A Large Health System: A Pilot Study, Andinet Alemu, Maharaj Singh, Chris Blumberg, John O. Richards, Martin K. Oaks, Michael A. Thompson

Maharaj Singh, PhD

Purpose

Common reasons for hospitalization and death in patients with multiple myeloma (MM) are infections. As patients with MM are living longer and are treated with immunomodulatory drugs, there is a need to immunize against vaccine-preventable diseases and ultimately determine the efficacy of these vaccines. We evaluated vaccination practice patterns in MM patients at our health system using electronic medical records and data analytics.

Methods

This institutional review board-approved study retrospectively reviewed patients with MM who visited the health system from May 2012 to May 2014. Data collected included demographics, influenza vaccination (FV) and pneumonia vaccination (PV) history, hospitalization episodes ...

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct ...

Blimp-1 Impairs T Cell Function Via Upregulation Of Tigit And Pd-1 In Patients With Acute Myeloid Leukemia., Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F. Claxton, W. Christopher Ehmann, Witold B. Rybka, Neil D. Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D. Schell, Raymond J. Hohl, Hui Zeng, Hong Zheng

Department of Medical Oncology Faculty Papers

BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML.

METHODS: Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of ...

Ido1 Is An Integral Mediator Of Inflammatory Neovascularization., Arpita Mondal, Courtney Smith, James B. Duhadaway, Erika Sutanto-Ward, George C. Prendergast, Arturo Bravo-Nuevo, Alexander J. Muller

Arturo Bravo-Nuevo

The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6). In this study, we investigated how genetic loss of IDO1 ...

A Review Of Autoimmune Diseases Associated With Cancer, Patricia Tai, Edward Yu, Kurian Joseph, Thomas Miale

Edward Yu

The focus of this review is on the relationships between autoimmune diseases and cancer from two closely related perspectives: 1.Those autoimmune diseases which are often associated with malignancies. 2.Those prevalent cancers which may increase the risks of developing autoimmune disorders. The review concludes with a brief discussion of some selected innovative approaches to cancer immunotherapy.

Robot Assisted Ultrasound Imaged Guided Interstitial Lung Brachytherapy In A Porcine Model, Richard A. Malthaner, Edward Yu, Jerry J. Battista, Chris Blake, Donal Downey, Aaron Fenster

Edward Yu

We set out to see if permanent interstitial brachytherapy seeds could be safely and reproducibly inserted thoracoscopicaly with the ZEUS Robotic system and intraoperative ultrasound into in-vivo porcine lungs.

Esophageal Cancer, Edward Yu

Edward Yu

No abstract provided.

A Review Of Autoimmune Diseases Associated With Cancer, Patricia Tai, Edward Yu, Kurian Joseph, Thomas Miale

Edward Yu

The focus of this review is on the relationships between autoimmune diseases and cancer from two closely related perspectives: 1.Those autoimmune diseases which are often associated with malignancies. 2.Those prevalent cancers which may increase the risks of developing autoimmune disorders. The review concludes with a brief discussion of some selected innovative approaches to cancer immunotherapy.

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations In Prostate Cancer., Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills

Kimmel Cancer Center, Presentations and Grand Rounds

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed ...